Antioxidants, pro-oxidants, and free radicals

Physician and health consultant Carsten Vagn-Hansen describes oxidation at the cellular level, which can, to some degree, be compared to rusting iron.

Oxidation is an electro-chemical reaction which can cause damage resulting in weakened or sick cells and can damage of the important proteins which compose the hereditary information (DNA) of the cells and control cell function. The result can be the conversion of a cell to a cancer cell or cell death.

Anything which inhibits oxidation is called an antioxidant.

Free radicalsThe transformation of oxygen in the body leads to the constant creation of free radicals, where one of the electrons, which normally come in pairs in the oxygen molecule, is pulled out of an oxygen molecule under a chemical reaction. An oxygen molecule with an unpaired electron becomes a free radical. This makes it necessary for the oxygen molecule to “steal” another electron to again become complete. This is done by stealing an electron from other molecules in proximity, which either are destroyed or become free radicals themselves. This can start a dangerous chain reaction leading to a cascade of damages. Antioxidants disrupt the free radicals’ chain reaction.

The free radicals attack everything in the body, both inside and outside of the cells. For example, if proteins, cell membranes, fats in the blood, and fatty acids on the cells’ surfaces are attacked, they become oxidized, or rancid, and the cell is weakened. They also attack “bad” LDL cholesterol and cause them to become rancid (a process also called lipid-peroxidation) and stick to and calcify the arteries as arteriosclerotic plaques. Cholesterol oxides are toxic. If the LDL cholesterol is not oxidized it is not harmful, but returns to the liver intact. Fat tissue is also especially prone to oxidation. This can be seen in the whole body, from the brain to the skin, which becomes dry, aged, wrinkled, or develops cancerous tumours.

The free radicals also attack the cells’ DNA (the controlling molecule of the cells) making the hereditary information seem moth-eaten. The cells contain a number of enzymes which constantly endeavour to repair DNA and maintain cellular health. The minerals selenium, zinc, copper, and manganese are contained in these enzymes. If the DNA is damaged, it changes its structure and mutates and can become cancer-DNA. Radiation, as well as solar radiation, increases the amount of free radicals, which can cause mutations which can lead to skin cancers such as melanoma.

Our genes control our cells. We have both good and bad genes, and none of the genes work unless they are activated (turned on). Viruses do not function either unless they are turned on.

Antioxidants counteract all of these processes and help maintain the cells’ and the body’s health. The free radicals are more likely to attack antioxidants than the substances that antioxidants protect, whereby the antioxidants become weak pro-oxidants, which are “renewed” to antioxidants by other antioxidants in the antioxidant network. The need for antioxidants increased greatly if exposed to chemical substances such as tobacco smoke, some of the 100,000 chemical substances we are exposed to each day, all sorts of additives in our food, or medicinal drugs. Aging can also be advanced by the lack of antioxidants.

It has been calculated that each cell in the body is exposed to about 10,000 attacks from free radicals each day, causing damage particularly to the cells’ genetic material. Age worsens this tendency. The elderly have as much as nine times as many mutations in their cells as a newborn. These dangerous free radicals play a large role in almost all diseases.

The antioxidant network – synergyAn authority on antioxidants, Richard Passwater, has said that we should not see antioxidants as solitary substances, but as cooperative players on a team or as single instruments in an orchestra. These are very good comparisons because there are many different antioxidants which work in different ways thus increasing each others’ effects considerably. This enables better results with lower doses of each individual antioxidant.

In the book “The Antioxidant Miracle,” the most important networking antioxidants are regarded to be lipoic acid, vitamin E, vitamin C, coenzyme Q10, and glutathione. These substances are helped by a number of natural substances including flavoniods from fruit and vegetables and pine bark (pycnogenol), as well as Ginkgo biloba, carotenes, and the mineral selenium which, though not an antioxidant itself, is necessary for the creation of enzymes with antioxidant effects. The same is true for zinc, copper, and manganese. Antioxidants are our personal inner doctor, who is constantly trying to maintain our health.

How can we protect ourselves from free radicalsFundamentally it is vital to avoid substances which lead to the creation of free radicals. These include tobacco smoke, all sorts of solvents, and other chemicals, especially the synthetic. Mercury amalgam, used in metallic tooth fillings, gives rise to the continuous production of free radicals. These are probably the most dangerous source and one of the most important causes of many chronic, degenerative illnesses because they are always in the mouth and always giving off mercury. There has been much serious research which proves that damage from amalgam fillings is real.

Exercise is good, but competition sports and overly strenuous exercise increases the production of free radicals (and weakens the immune system). Athletes therefore need many more antioxidants than non-athletes. Fresh air and clean water are also important. Americans are obsessed with getting completely fresh water, preferably distilled, to avoid the many metal ions and other pollutants found in drinking water. Metal ions, and not only mercury, are especially good at causing cascades of free radicals. Men should avoid too much iron intake.

It is also important to decrease stress, because stress increases the production of free radicals.

The dietThe diet is the most important source of natural antioxidants, which work together to fight free radicals. It has been abundantly proven that a diet rich in vegetables, fruit, and spices decreases the risk of getting cancer. It is recommended to eat about 600 gr. fruit and vegetables daily.

But despite a healthy diet, which few people abide to most of the time, it is difficult today to get sufficient levels of all of the important antioxidants. The soil in many areas contains too little selenium, which is the elemental basis of many important antioxidants. Many vegetables are grown intensively and quickly and cannot create all of the important antioxidants in sufficient levels. For example, in Holland it is common that vegetables grown on Rockwool or sawdust only are given artificial fertilizer and are exposed to strong artificial light 24 hours a day.

In addition, many of the foods that we buy contain a sea of chemical substances. Just look at the E-numbers, many of which are removed yearly when it is found that they are actually harmful to health.

There is therefore good reason to take extra supplements of antioxidants in the chemical and unnatural world which we live in. It is best to take them in their natural form, which besides a healthy diet is in the form of extracts from natural foods, for example from spices, leaves such as olive leaves, and fruits. We can just look to the apes. They eat the young leaves off the trees, and it has been shown that these leave contain many important antioxidants.

AntioxidantsThe most important antioxidants are lipoic acid, vitamin C, vitamin E, coenzyme Q10 and glutathione. When attacked by a free radical, vitamin E becomes a pro-oxidant, but it is recycled-renewed to an antioxidant by vitamin C, lipoic acid and Q10. Vitamin C is subsequently renewed by flavoniods, and together with vitamin E prevents the oxidation of fat in the blood found together with protein as lipoprotein. The network can be seen as self-restoring, where each part restores each other and works together.

Lipoic AcidLipoic acid strengthens the entire antioxidant network because it increases the levels of both vitamins C and E, glutathione, and Q10. It gives significant protection against stroke, where the damage is not caused, as most people believe, by lack to blood to the brain, but by cascades of free radicals released when the blood flow is returned. It has been shown quite neatly in an animal study that the damage to brain tissue is reduced greatly when the animals had been given lipoic acid after cutting off the blood supply for 30 minutes. Without lipoic acid 80 % of the rats died with 2 hours, but with lipoic acid only 25 % died within that period.

Lipoic acid also has a good effect for diabetics who have suffered nerve damage in the form of neuritis. A German researcher has shown that treatment with lipoic acid can stimulate the regeneration of nerve fibres in diabetics. Diabetes is a typical oxidative stress disease, and diabetics often have significantly lower levels of antioxidants than healthy people. Lipoic acid strengthens the immune system and betters the memory.

Vitamin CInsufficient vitamin C causes scurvy, which has throughout the ages killed many sailors and actually cropped up again a few years ago in Denmark when it was forbidden to add ascorbic acid to beer. Workers in the Tuborg and Carlsberg factories, some of which almost live on beer, came to their doctors with bleeding gums and excessive bruising, both symptoms of scurvy. Just one week of eating fruit and vegetables is enough to cure scurvy.

Vitamin C protects sperm cells against damage from free radicals, protects DNA from damage, and is critical for a normally functioning immune system. It is important for the collagen of the skin and protects against cataracts. It is a myth that it causes kidney stones and other problems. Particularly people with chronic illnesses like diabetes need extra vitamin C.

Vitamin EVitamin E is probably the greatest all-purpose antioxidant. It decresses the risks of blood clots in the heart and stroke (it is nonsense that it causes stroke), counteracts inflammation, keeps the skin young, and decreases the risk of prostate cancer. Vitamin E is not just a single vitamin, but a family of tocopherols and tocotienols.

Whereas tocopherols counteract oxidation of fats in the blood, tocotrienols have the ability to clean up calcification of arteries, such as the carotid arteries (arteries of the neck). In a study where participants were either given placebo or tocotrienols for a period of four years, the amount of calcification in their carotid arteries was measured over time with an ultrasound. 94 % of the participants who received tocotrienols showed improvement or were stabalised, whereas none of the controls showed improvement and some showed increased calcification.

Tocotrienols also seem to be a powerfull watchdog against both oestrogen positive and oestrogen negative breast cancer cells. The skin also loves tocotrienols. Vitam in E is also very important for immune function, which when weakened by age can be strengthened by vitamin E.

The brain is especially venerable for attack by free radicals because of its high blood flow and large fat content. In Alzheimer’s patients it is typical that there is a greater oxidization of fat than normal. This oxidation can be reduced by vitamin E.

A study where 341 patients with early Alzheimer’s were either given the new medicine, Selegilin or 2000 units vitamin E daily, both Selegilin and vitamin E, or placebo, showed that vitamin E alone had the greatest effect. The risk of developing Alzheimer’s was 53 % lower in the group that received vitamin E alone, 43 % lower in the group that received medicine alone, and 31 % in the group that both received vitamin E and the medicine.

Coenzyme Q10Q10 is a coenzyme which regenerates vitamin E in the antioxidant network. It is good for brain cells and can protect against Alzheimer’s and Parkinson’s diseases as well as deterioration in Lou Gehrig’s disease (ALS). It counteracts infection of the gums and might have good effects against breast cancer. It is produced in the body, but cancer and heart patients normally have low levels. Q10 is critical for energy production in the cells’ power plants, the mitochondria, and maybe especially heart muscle.

Amino acidsGlutathione contains sulphur and is produced in the body from three amino acids: cysteine, glutamic acid, and glycine, all of which are found in food. Fruit, vegetables, and freshly grilled meat contain glutathione, but it is broken down during digestion. Lipoic acid can increase the amount of glutathione greatly. Tobacco smoke, food with high chemical content, too much alcohol, as well as medications increase the need for glutathione, which is necessary for normal liver function and therefore detoxification of the body. Glutathione also improves immune function and reduces inflammation. The amount of glutathione falls considerably with age, but this can be counteracted.

Helping substances

Flavonoids

Falvonoids improve memory and concentration and are used to treat ADHD (attention deficit disorder). They are powerful antioxidants and refresh vitamin C. They are good for blood flow, keep the heart and circulation healthy, counteract blood clots, decrease inflammation, and improve immune function and male sexual function.
Flavonoids are part of the polyphenol group, all of which are antioxidants. A blend of flavonoids, which can be found in Gingko biloba and pine bark extract (pycnogenol), is more powerful than one flavonoid alone. The same is true of olive leaves. This effect is called synergy.

Tea is full of flavonoids, and the long lifespan of the Japanese, despite smoking, pollution, and stress, is largely attributed to their prolific tea drinking habits. Green tea is stronger than black tea in this respect. Red wine also contains large amounts of flavonoids, and is better than white wine for prevention. Extracts from the seeds of red grapes (proanthocyanidins) have an antioxidant effect which is many hundred times greater than that of vitamin C. The same is true of many spices, including oregano.

Many people suffering from chronic tiredness have reported good effects from using pycnogenol (pine bark). This is completely safe to use.

Lycopene, which is especially found in tomatoes which have been boiled and in tomato ketchup, can prevent prostate cancer. A study from Israel has shown that lycopene inhibits cancer cell growth in breast cancer and lung cancer. Lutein and zeaxanthin drecrease the risk of macula degeneration, which is also known as calcification of the eye.

As mentioned, the important minerals selenium, zinc, copper, and manganese, also have a helping function by being a part of the enzymes that are antioxidants. Many people have deficiencies of these minerals.

CarotenesCarotenes, which are the precursor of vitamin A, are natural pigments. Hundreds of them exist, including 60 in our food. Researchers have concentrated their efforts on alpha-carotene, beta-carotene, crytoxanthine, lutein, lycopene, and zeaxanthin. Brightly coloured fruit and vegetables are rich in carotenes.

Beta-carotene can strengthen immune function in the elderly, but a mix of carotenes is better. All in all it seems that increased intake of food with high carotene levels increases protection against many forms of cancer. When beta-carotene comes from a diet rich in fruit and vegetables, there is, contrary beta-carotene from artificial supplements, no increased risk of lung cancer.

SulphurSulphur plays a large role as an ingredient of important substances with antioxidant effects; such as glutathione and the amino acids L-cysteine and methionine, which work together with vitamins C and E and coenzyme Q10 (which is found naturally in the body) in the antioxidant network. Glutathione is the most commonly found antioxidant in the network and is found in almost all cells. The production of glutathione begins to fall from the age of 40. A good source of sulphur is the substance MSM (methylsulfonylmethane), which is approved for human use in the USA.

Pro-oxidantsOxidation can also be beneficial. The immune system uses free radicals in the fight against viruses and bacteria. If bacteria come into the body (the bacteria on the surface of the body and in the intestines are normally beneficial and necessary), they are quickly found by white blood cells, which send a cascade of free radicals against the bacteria leading to their destruction. This harms the cells in the area, but they are quickly repaired. People with cold sores can follow this process directly. First they are itchy, then they form blisters followed by redness and infection, after which they dry out and disappear. If the white blood cells’ “bombardment” of free radicals misses its target it can cause tissue damage, which can be seen in arthritis and other autoimmune diseases where the immune system attacks the body itself.

Free radicals are also important for our brain function, our sex life, and for our ability to kill cancerous cells. There therefore must be a good balance between free radicals and antioxidants.

There are a lot of pro-oxidants in our surroundings in the form of large amounts of chemicals, so normally the biggest problem is getting enough antioxidants. Therefore it is important to get enough antioxidants through a healthy diet and supplements, as well as reduce the effects of the pro-oxidants in our environment which can harm us. We should avoid the many metal ion pro-oxidants, not least, as mentioned, mercury amalgam in fillings. This includes excess iron in the body.

Some cell toxic substances used for chemotherapy and against some autoimmune diseases are pro-oxidants. Antioxidants can, as mentioned, be attacked and become pro-oxidants, but these pro-oxidants are weak and are quickly regulated by the body.

Some cancer doctors advise their patients against taking antioxidants while undergoing chemotherapy, but many studies have shown that free radicals play an important part in the development of cancer, and that antioxidants, which destroy free radicals, help fight cancer. Cancer cells also produce large amounts of free radicals which send signals promoting further uncontrolled growth. This is supported by a study from John Hopkins Medical Institution published in Science on March 14, 1997.

Studies involving growing cancer cells outside of the body have also shown that a grape seed extract from red grapes (ActiVin ®) can inhibit the growth of many types of cancer cells while encouraging the growth of normal cells.

No studies have shown that antioxidants have the ability to disturb cancer treatment. This hypothesis is only supported by test-tube studies where cells were grown outside of the body. On the other hand, vitamin C has been shown to improve the effectiveness of chemotherapy in animals and in a study on human breast cancer cells outside of the body.

A modified form of vitamin A has been shown to work synergistically (strengthen each others effectiveness) with normal cancer treatment in test-tube studies. A summary of research in this field (Cancer Treatment Rev 1997;23:209-4) has concluded that it is not necessary to avoid antioxidants due to fears that they will disturb the effects of chemotherapy.

In an Italian study from 1996, 30 patients with brain tumours received either radiation therapy or the hormone melatonin, which is a powerful antioxidant. The survival rate was higher in the group which received melatonin. A clinical trail has shown that treatment with antioxidants combined with chemotherapy and radiation increases the survival rates of patients with small cell lung cancer when compared to most published results of treatment with combined chemotherapy and radiation alone (Anticancer-Res. 1992 May-Jun; 12(3):599-606).

In Denmark, Dr. Knud Lockwood and others undertook a controversial study where 32 women with breast cancer which had spread to other parts of the body were treated with a number of antioxidants. None of the women died at the study’s finish (it was expected that four would die), none showed signs of further spreading, there was improved quality of life, and six patients shown partial remission.

An important thing which antioxidants can bring about is a decrease of the risk of DNA damage in healthy cells. It is well known that chemotherapy and radiation, which also releases many free radicals, increase the risk of cancer later in life. This is due to damage of the DNA. The most common cancer caused in this manner is leukaemia, which is not uncommon 4-5 years after treatment of the original cancer.

Antioxidants such as vitamin E increase have been shown to increase the effectiveness of chemotherapy. The flavonoid genisteine from soy beans has been shown to increase the build up of some chemotherapy drugs in cancer cells and another flavonoid, quercetin, has been shown to increase many chemotherapy drugs toxic effects on cancer cells. Nevertheless, clinical studies on these substances’ effects on cancer chemotherapy are lacking.

In a comprehensive review of the problems regarding nutrition and cancer it was concluded that dietary supplements of antioxidants can be a safe and effective way to increase the effectiveness of cancer chemotherapy. Patients’ quality of life can be improved by supplementing the diet with antioxidants, which reduce or prevent the side effects of chemotherapy.

Japanese researcher showed in a randomised trial that a combination of three antioxidants, vitamin E, vitamin C and N-acetyl cysteine, protected against chemotherapy related heart damage without reducing the effectiveness of the chemotherapy. It would be nice if doctors all over Europe were more interested in antioxidants.

All in all much indicates that it is good to combine chemotherapy treatment with a healthy diet rich in fruit and vegetables and supplements of antioxidants. Taking many different antioxidants creates a synergy; a cooperation between the antioxidants which increase each others effects. It is not a good idea to overdo anything, not even antioxidants, and it is best to take them in their natural form.

A Japanese study of the natural cell killing activity of white blood cells (lymphocytes) showed increased activity with a decrease of chemical stress on the body, especially with quitting smoking. The results of the study show a relationship between a natural immune system and reduced incidence of common cancers.

In summary it is established that the antioxidant network and its many aids keep the body’s cells and the body itself in good shape, prevent aging, increases resistance against cancer and cardiac diseases, as well is good for brain function and prevents dementia. It is also important for detoxification of the body (especially glutathione).

First and foremost, we should try to have a healthy and balanced diet with at least 600 grams fruit and vegetables daily. Supplements of single antioxidants can help, but are not good enough alone. Fresh vegetables and fresh fruit are the best choice, especially if organic.

One should also try to avoid chemicals as much as possible and try to keep percent of fat in the diet lower than 30. These fats should be fluid, healthy oils such as olive oil, fish oil, borage oil, and evening primrose oil, as well as the fats found in plants.

Free radicals play a role in the rise and development of almost all known diseases. By strengthening the body’s antioxidant network we can give the body a weapon which it can use to fight an effective war against disease.

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You can read more in the books:
"The Antioxidant Miracle" by Lester Packer og Carol Colman (1999. John Wiley and Sons. ISBN 0-471-29768-2)